The annual incidence of reported infections by Neisseria gonorrhoeae (N.g.) is estimated to be about two million cases. A gonococcal infection in men usually results in a relatively uncomplicated urogenital infection. Disseminated gonococcal infection is reported to occur in 1 to 3% of those with gonorrhea, but the morbidity of this disease with current therapy is slight.
On the other hand, in women infected with gonorrhea, salpingitis occurs in 10 to 20%, and even when adequately treated, may result in recurrent salpingitis, ectopic pregnancy, and infertility. It is estimated that salpingitis leads to 1.8 million office visits to private physicians and 220,000 hospitalizations each year in the United States.
The control of gonorrhea by public health measures to date has been difficult. A vaccine composed of whole, killed gonococci has not been efficacious, Greenburg et al. "Preliminary Studies on the Development of a Gonococcal Vaccine," Bull. Wld. Hlth. Org. 45:531 (1971).
Penicillin and tetracycline resistant strains of gonococci have also emerged.
Gonococcal infection involves colonization of the mucous membranes by the bacterium, a process mediated by the adhesion of the colonizing cell to the surface membrane. The term "adhesion" describes the relatively stable attachment of bacteria to surfaces. Any structures responsible for such adhesive activities are termed adhesins.
The gonococcal pilus is an adhesin having a filamentous structure composed of repeating identical subunits (pilin). In the MS11 strain of N.g., each pilin has a molecular weight of approximately 18,000 daltons. The attachment of the gonococci to the epithelial surface can be blocked by an anti-pilus antibody. In addition to blocking cell attachment, antibodies raised against pilus protein are also opsonic, i.e., they mediate the killing of the invading bacteria by the phagocytes in the blood. However, the use of pilus immunogens as vaccines has been rendered impractical by the lack of serological cross-reactivity of pili made by different strains of N.g.
We have found that eukaryotic cell surface glycosphingolipids, e.g., lactosylceramide, isoglobotriosylceramide, gangliotriosylceramide, and gangliotetraosylceramide, are involved in recognition and adhesion of N.g., and further that the glycolipid-directed recognition is mediated by a heretofore unreported bacterial lectin, a bacterial protein having the ability to recognize and bind to specific saccharide sequences (carbohydrate structures). This bacterial lectin, when used as a constituent of an inoculum, a vaccine, or in a diagnostic assay, does not suffer from the aforementioned shortcomings of a pilus immunogen.